Mevalonate dependency of the early cell cycle mitogenic response to epidermal growth factor and prostaglandin F2α in Swiss mouse 3T3 cells
Lovastatin (LOV), a hydroxy‐methylglutaryl‐coenzyme A (HMGCoA) reductase competitive inhibitor, blocks epidermal growth factor (EGF)— or prostaglandin F2α (PGF2α)—induced mitogenesis in confluent resting Swiss 3T3 cells. This inhibition occurs even in the presence of insulin, which potentiates the a...
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todo:paper_00219541_v162_n1_p139_Ortiz2023-10-03T14:23:36Z Mevalonate dependency of the early cell cycle mitogenic response to epidermal growth factor and prostaglandin F2α in Swiss mouse 3T3 cells Ortiz, M.B. Goin, M. de Alzaga, M.B.G. Hammarstrom, S. de Asua, L.J. cholesterol dolichol epidermal growth factor insulin mevalonic acid mevinolin prostaglandin f2 alpha tunicamycin ubiquinone animal cell article cell cycle cell strain 3t3 controlled study mitogenesis mouse nonhuman priority journal 3T3 Cells Animal Dinoprost Dose-Response Relationship, Drug Epidermal Growth Factor Glycosylation Lovastatin Mevalonic Acid Mice Mitosis S Phase Support, Non-U.S. Gov't Animalia Lovastatin (LOV), a hydroxy‐methylglutaryl‐coenzyme A (HMGCoA) reductase competitive inhibitor, blocks epidermal growth factor (EGF)— or prostaglandin F2α (PGF2α)—induced mitogenesis in confluent resting Swiss 3T3 cells. This inhibition occurs even in the presence of insulin, which potentiates the action of these mitogens in such cells. LOV exerts its effect in a 2–80 μM concentration range, with both mitogens attaining 50% inhibition at 7.5 μM. LOV exerted its effect within 0–8 h following mitogenic induction. Mevanolactone (10–80 μM) in the presence of LOV could reverse LOV inhibition within a similar time period. LOV‐induced blockage of PGF2α response is reflected in a decrease in the rate of cell entry into S phase. Neither cholesterol, ubiquinone, nor dolichols of various lengths could revert LOV blockage. In EGF‐ or PGF2α‐stimulated cells, LOV did not inhibit [3H]leucine or [3H]mannose incorporation into proteins, while tunicamycin, an inhibitor of N′ glycosylation, prevented this last phenomenon. Thus, it appears that LOV exerts its action neither by inhibiting unspecific protein synthesis nor by impairing the N′ glycosylation process. These findings strongly suggest that either EGF or PGF2α stimulations generate early cell cycle signals which induce mevalonate formation, N′ glycoprotein synthesis, and proliferation. The causal relationship of these events to various mechanisms controlling the onset of DNA synthesis is also discussed. © 1995 Wiley‐Liss, Inc. Copyright © 1995 Wiley‐Liss, Inc. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00219541_v162_n1_p139_Ortiz |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
cholesterol dolichol epidermal growth factor insulin mevalonic acid mevinolin prostaglandin f2 alpha tunicamycin ubiquinone animal cell article cell cycle cell strain 3t3 controlled study mitogenesis mouse nonhuman priority journal 3T3 Cells Animal Dinoprost Dose-Response Relationship, Drug Epidermal Growth Factor Glycosylation Lovastatin Mevalonic Acid Mice Mitosis S Phase Support, Non-U.S. Gov't Animalia |
| spellingShingle |
cholesterol dolichol epidermal growth factor insulin mevalonic acid mevinolin prostaglandin f2 alpha tunicamycin ubiquinone animal cell article cell cycle cell strain 3t3 controlled study mitogenesis mouse nonhuman priority journal 3T3 Cells Animal Dinoprost Dose-Response Relationship, Drug Epidermal Growth Factor Glycosylation Lovastatin Mevalonic Acid Mice Mitosis S Phase Support, Non-U.S. Gov't Animalia Ortiz, M.B. Goin, M. de Alzaga, M.B.G. Hammarstrom, S. de Asua, L.J. Mevalonate dependency of the early cell cycle mitogenic response to epidermal growth factor and prostaglandin F2α in Swiss mouse 3T3 cells |
| topic_facet |
cholesterol dolichol epidermal growth factor insulin mevalonic acid mevinolin prostaglandin f2 alpha tunicamycin ubiquinone animal cell article cell cycle cell strain 3t3 controlled study mitogenesis mouse nonhuman priority journal 3T3 Cells Animal Dinoprost Dose-Response Relationship, Drug Epidermal Growth Factor Glycosylation Lovastatin Mevalonic Acid Mice Mitosis S Phase Support, Non-U.S. Gov't Animalia |
| description |
Lovastatin (LOV), a hydroxy‐methylglutaryl‐coenzyme A (HMGCoA) reductase competitive inhibitor, blocks epidermal growth factor (EGF)— or prostaglandin F2α (PGF2α)—induced mitogenesis in confluent resting Swiss 3T3 cells. This inhibition occurs even in the presence of insulin, which potentiates the action of these mitogens in such cells. LOV exerts its effect in a 2–80 μM concentration range, with both mitogens attaining 50% inhibition at 7.5 μM. LOV exerted its effect within 0–8 h following mitogenic induction. Mevanolactone (10–80 μM) in the presence of LOV could reverse LOV inhibition within a similar time period. LOV‐induced blockage of PGF2α response is reflected in a decrease in the rate of cell entry into S phase. Neither cholesterol, ubiquinone, nor dolichols of various lengths could revert LOV blockage. In EGF‐ or PGF2α‐stimulated cells, LOV did not inhibit [3H]leucine or [3H]mannose incorporation into proteins, while tunicamycin, an inhibitor of N′ glycosylation, prevented this last phenomenon. Thus, it appears that LOV exerts its action neither by inhibiting unspecific protein synthesis nor by impairing the N′ glycosylation process. These findings strongly suggest that either EGF or PGF2α stimulations generate early cell cycle signals which induce mevalonate formation, N′ glycoprotein synthesis, and proliferation. The causal relationship of these events to various mechanisms controlling the onset of DNA synthesis is also discussed. © 1995 Wiley‐Liss, Inc. Copyright © 1995 Wiley‐Liss, Inc. |
| format |
JOUR |
| author |
Ortiz, M.B. Goin, M. de Alzaga, M.B.G. Hammarstrom, S. de Asua, L.J. |
| author_facet |
Ortiz, M.B. Goin, M. de Alzaga, M.B.G. Hammarstrom, S. de Asua, L.J. |
| author_sort |
Ortiz, M.B. |
| title |
Mevalonate dependency of the early cell cycle mitogenic response to epidermal growth factor and prostaglandin F2α in Swiss mouse 3T3 cells |
| title_short |
Mevalonate dependency of the early cell cycle mitogenic response to epidermal growth factor and prostaglandin F2α in Swiss mouse 3T3 cells |
| title_full |
Mevalonate dependency of the early cell cycle mitogenic response to epidermal growth factor and prostaglandin F2α in Swiss mouse 3T3 cells |
| title_fullStr |
Mevalonate dependency of the early cell cycle mitogenic response to epidermal growth factor and prostaglandin F2α in Swiss mouse 3T3 cells |
| title_full_unstemmed |
Mevalonate dependency of the early cell cycle mitogenic response to epidermal growth factor and prostaglandin F2α in Swiss mouse 3T3 cells |
| title_sort |
mevalonate dependency of the early cell cycle mitogenic response to epidermal growth factor and prostaglandin f2α in swiss mouse 3t3 cells |
| url |
http://hdl.handle.net/20.500.12110/paper_00219541_v162_n1_p139_Ortiz |
| work_keys_str_mv |
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